Use of inhaled corticosteroids and long acting beta agonist (ICS/LABA) combination therapy has been shown to decrease the frequency of exacerbations in patients with chronic obstructive pulmonary disease (COPD). In this population, adherence to treatment is associated with better disease control and lower risk of COPD-related exacerbations in the future. Using a treatment with a more convenient regimen or easier-to-use device could improve patient adherence, improve disease control, decrease the frequency of exacerbations and minimize the COPD-related economic burden. Real-world information on the impact on healthcare costs and exacerbation risk of initiating once-daily or twice daily ICS/LABA in this patient population is limited. The objective of this study was to assess COPD-related healthcare costs, adherence, and exacerbations in COPD patients initiating treatment with fluticasone furoate/vilanterol 100/25 (FF/VI) or budesonide/formoterol 160/4.5 (BUD/F) using a large managed care database in the US.